What Is Castration-Resistant Prostate Cancer (CRPC)?

Castration-resistant prostate cancer (CRPC) means that the disease fails to respond to treatment and progresses. It includes situations in which the cancer continues to progress despite reduced testosterone levels. Treatment generally aims to prevent spread to other parts of the body.

Prostate cancer normally needs suitable testosterone levels to grow. Treatments such as surgical removal of the testicles or hormone-blocking therapy greatly reduce testosterone, slowing cancer progression. CRPC occurs when cancer does not respond to low, castrate testosterone levels, generally defined as less than 50 nanograms per deciliter.

Cancer that has not spread is generally easier for specialists to treat. CRPC treatment therefore aims to prevent spread elsewhere, such as to the bones or lymph nodes.

Symptoms of Castration-Resistant Prostate Cancer

Patients with early-stage CRPC that has not spread generally have no symptoms. Symptoms may, however, develop and prompt diagnosis. A 2016 study found that approximately 60% of patients with nonmetastatic CRPC progressed to metastatic CRPC within 5 years.

Symptoms of metastatic CRPC may include fatigue, burning or pain during urination, an increased need to urinate, a weak or interrupted urine stream, pain during ejaculation, blood in semen or urine, vomiting, weakness, loss of appetite, anxiety, sleep problems and cognitive changes.

90% of patients with CRPC develop bone metastases . These may cause fractures, bone pain and spinal cord or nerve compression.

Diagnosing Castration-Resistant Prostate Cancer

CRPC is generally diagnosed in people already diagnosed with prostate cancer. Specialists then order tests to monitor the patient's condition and assess treatment effectiveness. Prostate examination, blood tests and imaging scans may also determine the cancer's stage and whether it has spread.

Staging and Grading

Specific scans are needed to stage CRPC when it has spread. Prostate cancer stage depends on the primary tumor's size and whether cancer has reached lymph nodes or other parts of the body. If it has not spread, its aggressiveness is assessed. This involves considering the PSA (prostate-specific antigen) doubling time . This helps determine how rapidly the cancer may spread and which treatment is most effective.

Management and Treatment of Castration-Resistant Prostate Cancer

Treatment for castration-resistant prostate cancer (CRPC) varies with its stage and extent of spread, particularly whether it is metastatic. The size of the primary tumor and the sites of spread can also influence treatment options.

Treatment of Nonmetastatic CRPC

In nonmetastatic CRPC, the patient has high PSA levels despite castrate testosterone levels, and cancer has not spread elsewhere in the body. Treatment generally includes:

• Injections that block testosterone production
• Drugs that block androgen receptors

Doctors may also recommend other hormone treatments, including antiandrogens such as enzalutamide or apalutamide. Alternatively, they may temporarily stop antiandrogen treatment and observe its effects on the patient.

Treatment of Metastatic CRPC

Treatment options for metastatic CRPC generally include:

• Hormone Therapy: Antiandrogens, androgen synthesis inhibitors and other hormone treatments.
• Radiation Therapy: Used to relieve symptoms, destroy cancer cells and manage urinary problems.
• Chemotherapy: Used to manage symptoms and reduce cancer cells.
• Targeted Therapy: Drugs that target specific cells or molecules to stop cancer cells from growing and spreading.

Metastatic CRPC also commonly spreads to the bones. Treatments for metastatic bone cancer generally include:

• Corticosteroids: Reduce inflammation.
• Painkillers: Relieve bone pain.
• Bone-Modifying Agents: Strengthen bones and prevent weakening, for example bisphosphonates.
• Kyphoplasty: Stabilizes collapsed bones. Also called cementing.
• Radiation Therapy: Shrinks or destroys cancer cells.

Castration-Resistant Prostate Cancer and Survival 

Nonmetastatic CRPC generally becomes metastatic within 3-5 years. The 5-year survival rate for metastatic CRPC is approximately 30%, meaning around 30% of patients may live for at least 5 years after diagnosis. In contrast, the 5-year survival rate for early-stage prostate cancer that has not spread is 99%.

In conclusion, CRPC is prostate cancer that continues growing even when testosterone levels are extremely low. Management may include hormone therapy, radiation therapy, chemotherapy and targeted treatments, generally tailored to the individual's circumstances. This metastatic cancer commonly spreads to bones, causing symptoms such as bone pain and fractures.

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